The present invention relates to protected active compound formulations of amino acids, in particular methionine, and of vitamins, pigments or enzymes and a process for the preparation of these protected active compound formulations. This invention relates in particular to active compound formulations of amino acids which are suitable for providing amino acids in a rumen-protected form for the nutrition of stock animals, in particular ruminants. In a further aspect, the present invention relates to feedstuff containing the protected active compound formulations and method of using same.
Methionine or its substitute, the methionine hydroxy analogue, have been employed very successfully for decades in animal nutrition as additives for meeting the requirement of stock animals for the essential amino acid in a economical but also in a physiologically and ecologically optimum manner. However, methionine or also the hydroxy analogues cannot be employed directly in the nutrition of ruminants, since the microbes living in the rumen metabolize amino acids, hydroxy acids and proteins relatively rapidly. If unprotected amino acids or hydroxy acids are fed to ruminants, the predominant proportion of these amino acids or hydroxy acids would therefore not be available to the ruminant for its own supply, but would be lost for protein synthesis in metabolism by microbial breakdown in the rumen.
A large number of so-called rumen-protected products are known in the prior art, but a predominant number thereof are not stable enough to microbial breakdown in the rumen to ensure an appropriate use as an additive. The best products to date are based on the use of relatively large shaped pieces of methionine, such as, for example, granules or pellets, which are protected by coating with polymers. Ethylcellulose (EP 0 495 349) or a copolymer of vinylpyridine and styrene (U.S. Pat. No. 4,877,621 and U.S. Pat. No. 4,876,097) is used, for example, as the coating composition.
The products described in EP 0 495 349 comprise a shaped piece of methionine which is obtained by pelleting methionine and auxiliary substances and is then coated with a protective shell of ethylcellulose, preferably in 2-layer application with an inorganic auxiliary substance or filler (e.g. sodium aluminum silicate). The cylindrical shape of the pellets resulting from the preparation leads to edges with a relatively thin coating, which are regarded as intentional breaking points and as essential for the release of the active compound.
EP 0 495 349 (comparison example 5) furthermore reports that rounded-off particles with a uniformly thick film thickness show adverse effects.
The products obtained in EP 0495 349 release methionine in the entire digestive tract, relatively little in the rumen, which can be seen from the high in vitro rumen protection of ≧80%, but increasingly more in the further digestive tract of the abomasum and small intestine. These delayed release properties, also called “slow release” properties, are preferred here since a small introduction of methionine in the rumen stabilizes the rumen flora. This is favorable overall, and a slow uniform release of methionine in the further course of digestion leads to a more uniform utilization than a sudden pH-controlled release in the abomasum at pH 2, which is aimed for with the products from U.S. Pat. No. 4,877,621 and U.S. Pat. No. 4,876,097.
On the basis of the size of the particles shown in EP 0 495 349 of approx. 3.5 mm length, however, stable homogeneous distribution of such products in feed mixtures is not always easy to achieve, on the one hand because of the small number of particles, due to the size, per volume and on the other hand because of the difference in size with respect to the other mixed feed components, which can lead to demixing in some cases under adverse conditions. On the other hand, there is no mechanical stability when exposed to very high stresses, such as e.g. during pelleting of the feed.
The protected products described in U.S. Pat. No. 4,877,621 and U.S. Pat. No. 4,876,097 are based on coating of pellets which comprise amino acids and have diameters of 0.1 to approx. 5 mm, a pH-sensitive protective shell being built up. Since the intention is to produce pH-dependent release properties, a copolymer of 2-vinylpyridine and styrene is always used here as an essential constituent, and in U.S. Pat. No. 4,876,097 additionally further components, such as e.g. zein cellulose acetobutyrate, polyvinyl acetate, chitosan, ethylcellulose and further auxiliary substances, including various solvents, which leads to a complicated protective shell comprising several components. The release properties indeed show entirely good results, but are achieved at the expense of a high complexity and by the use of coating or auxiliary substances which in some cases have not yet been approved in feedstuffs legislation, which makes economical utilization difficult.
EP 0 614 615 relates to a feedstuffs additive of a rumen-protected composition which comprises a biologically active substance and a protective shell and furthermore also has a pelleting-resistant protective shell of natural or synthetic polymers. Polymers which are suitable for this pelleting-resistant protective shell have an elasticity modulus at 30° C. of between 108 and 1011 dynes/cm2 and a glass transition temperature of between 50° C. and 150° C. This composition comprises pelleted granules with a particle size of greater than 1.5 mm.
U.S. Pat. No. 5,290,560 describes a process for the preparation of granules by extrusion with food or medicament active compounds for ruminants, in which the core of the granules is extruded in a first step and the core is coated by pulverization in a second step.
EP 588 346 describes a process for the preparation of 1.5 mm granules by extrusion with food or medicament active compounds for ruminants, in which the core of the granules is extruded in a first step and the core is coated by fluidized bed coating in a second step. The feedstuffs additive composition for ruminants described here comprises a coated core of the biologically active substance. The biologically active substance is an amino acid, such as e.g. lysine or methionine. The coating material comprises hydrogenated animal fat, oil or wax and an aliphatic monocarboxylic acid and/or nucleic acid, nucleotides, nucleosides, bases containing nucleic acid or salts.
In view of the problems described, it was an object to provide an active compound formulation which does not have the above-mentioned disadvantages of the existing products or has them to a significantly smaller extent and shows the advantages of the “slow release” properties described in EP 495349, that is to say an increased release after >6 h (≅residence time in the rumen).
One possibility of achieving the object described chiefly comprises coating of significantly smaller particles. However, this possibility on the one hand has the disadvantage of increased consumption of often relatively expensive coating compositions. On the other hand, multi-layer application with additional components (fillers), which allow later dissolution of the protective shell at the desired place, such as is necessary in the case of the products described in EP 0 495 349, can scarcely be realized with very small particles (see EP 0 614 615, comparison examples 1-6).